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Biomedical subjects

M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 19 recordsLinked to original sources
PubMed1992

The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1.

To identify the principal neutralization determinant (PND) of simian immunodeficiency virus (SIV), antisera were generated using recombinant gp110 [the SIV analog of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein, gp120], gp140, several large recombinant and proteolytic envelope fragments, and synthetic peptides of the SIVmac251 isolate. When purified under conditions that retain its native structure, gp110 bound CD4 and elicited antisera that neutralized SIVmac251 with high titer. Native gp110 also completely inhibited neutralizing antibody in sera from SIVmac251-infected macaques. In contrast, denatured gp110 and gp140, large envelope fragments, and synthetic peptides (including peptides analogous to the HIV-1 PND) elicited very low or undetectable neutralizing antibody titers and did not inhibit neutralizing antibody in infected macaque sera. Enzymatically deglycosylated gp110 efficiently absorbed neutralizing antibodies from macaque sera, showing that neutralizing antibodies primarily bind the protein backbone. A 45-kDa protease digest product, mapping to the carboxyl-terminal third of gp110, also completely absorbed neutralizing antibodies from infected macaque sera. These results show that the PND(s) of this SIV isolate depends on the native conformation and that linear peptides corresponding to the V3 loop of SIV envelope, in contrast to that of HIV-1, do not elicit neutralizing antibody. This may affect the usefulness of SIVmac for evaluating HIV-1 envelope vaccine approaches that rely on eliciting neutralizing antibody.

Antigens, Viral↗
PubMed1992

Goserelin depot in the treatment of premenopausal advanced breast cancer.

333 pre- and peri-menopausal patients with breast cancer entered a programme of open studies on the effect of goserelin. Of the 333 patients, 265 patients were entered into assessable efficacy studies. Efficacy data were analysed from 228 eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous injection of a depot formulation once every 28 days. Mean serum luteinising hormone (LH) and oestradiol concentrations were suppressed by day 22 after the first injection. Subjective response occurred in 68.3% of patients assessed. Objective response (UICC criteria) occurred in 36.4% of patients and the lifetable median duration of response was 44 weeks. Responses were observed in all histological grades of tumour, and regardless of oestrogen receptor status. Treatment was well tolerated with no withdrawals due to possible adverse reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly encountered. Goserelin provides an effective well tolerated medical alternative to ovarian ablation in the management of advanced breast cancer.

Adult↗
PubMed1992

[Three-dimensional ultrasound imaging of benign and malignant breast tumors--initial clinical experiences].

Previous experimental and clinical studies showed, that three-dimensional (3-D), i.e. dynamic spatial reconstruction of 2-D ultrasound images is feasible. A rotating acoustic plane helps to visualise the cross-sections serially and in a coordinated manner. When reconstructing the 2-D ultrasound images, surface reconstruction from planar contours of each cross-section is performed (so that the organ limits are defined) and the cross-sectional pictures are reconstructed into 3-D organ images. This approach had been described by the authors on a previous occasion. Another step forward is "transparent" spatial imaging eliminates the source of error involved in contouring. It is important to emphasise, that the 3-D system now described by the authors, yields a spatial image of the organ in question, and does not just present 3 planes of the organ (some authors have been claiming, that such an imaging method is also three-dimensional). Our system enables the imaging of several cross-sectional planes cut through the spatially calculated organ. This results in cross-sections, which cannot be performed by conventional sonography, thus disclosing new perspectives and possibilities. In the present article, the authors describe a clinical pilot study in the diagnosis of carcinomas of the breast. In our opinion, 3-D imaging of the tumours enables the physician to diagnose the status of the tumours; this is demonstrated by the examples of 35 malignant and benign tumours of the breast. In 95% of the cases of malignant tumours and 80% of the benign tumours, the diagnosis proved correct. This paper describes the fundamental possibilities and limitations of the new method.

Breast Neoplasms↗
PubMed1992

[B-streptococci in obstetrics--risks and consequences of maternal colonization and neonatal contamination].

2,373 mothers and their newborn were studied during two years with respect to B streptococci colonisation or contamination. Bacteriological, vaginal and anal smears were taken from mothers at the beginning of parturition, as well as the amnion and the aspirated stomach contents of the newborn, employing, in each case, conventional culture methods and a latex agglutination test as a rapid testing method. Smears from the ears were also taken from the newborn for bacteriological examination. The vertical transmission and its possible influencing variables were examined in 1,328 mother/child pairs of the first observation year. Surface contamination of the newborn was confirmed in 10% in at least one smear. In the group of mothers with B streptococci colonisation, the amnion showed the highest rate of contamination (43%), followed by the aspirated stomach contents (26%) and the ear smears (taken from each side separately) with 28% and 30% respectively. Vertical transmission was decisively influenced by vaginal maternal colonisation (50% of the cases resulting in contamination of newborn), whereas anal colonisation, if it was the only site of colonisation, resulted in contamination of newborn in only 32% of the cases. The rate of contamination of newborn dropped significantly from 50% to 20% after intrapartal antibiotic prophylaxis, the latter appearing to be meaningful only after at least 6 hours of exposure. In this group, the surface contamination could be reduced from 61% to 8%. A group of newborn suffering from early onset of sepsis (0.4%), was compared with a group of 13 newborn at risk of infection (0.9%) with established surface contamination and clinical or laboratory chemistry confirmation of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗
PubMed1992

[Ultrasound diagnosis of blood flow in benign and malignant breast tumors].

Malignant tumours can be differentiated from the benign ones by their vascular blood supply. We employed three methods to analyse the blood flow: the angiodynograph, the duplex system, and the continuous-wave Doppler method, and measured the blood flow in 151 patients on the preoperative day. Histology revealed a malignoma in 92 cases and a benign tumour in 59 cases. It was found, that in more than 90% of the malignomas, a high blood flow was identified in or around the tumour by means of the colour method (angiodynography), which could be quantified by the pulsed-wave Doppler. A significantly lower blood flow was evident in the benign tumours with a markedly increased resistance index (by 80%) established by means of the pulsed-wave Doppler. Continuous-wave (CW) Doppler showed a significantly higher blood flow with almost all malignomas in the entire breast, than was the case with benign changes. Our studies showed, that the enhanced blood flow in and around malignant tumours can be visualised by means of update technology, angiodynography being particularly suitable for demonstrating the flow by the B-mode. Quantification, however, is, at present, only possible by employing the duplex method with pulsed-wave Doppler. CW Doppler is suitable only for blood flow diagnosis of the entire organ, but it requires great precision of working method and is time consuming; tumour blood flow cannot be visualised on-target by this method.

Blood Flow Velocity↗
PubMed1992

[Palliative laser therapy in gynecologic oncology].

Local recurrences of carcinomas of the breast and genitals are a severe psychic and physical strain on the patients. Continuous confrontation with an often visible and generally painful tumour manifestation is an indication for palliative treatment, if other oncological therapies can no longer be employed. In these cases, the possibility of laser use represents a new therapeutic approach. In a pilot study at the University of Heidelberg, Department of Obstetrics and Gynaecology, a palliative laser therapy was performed on 45 patients with locally recurrent carcinomas of the breast (n = 29) and genitals (n = 16). Carbon dioxide and Nd:YAG lasers were utilized for tumour resection, vaporisation and coagulation. This new concept, the combined application of both wavelengths has been proved to be most efficient.

Adult↗
PubMed1992

[Diagnosis of tubal function using intraluminal ultrasound--initial results].

The extremely small ultrasound transducers of the intraluminal ultrasound instruments, introduced via catheters, enable diagnosis to be made inside hollow organs. In order to test the possible uses and indications for this new method in gynaecology, we conducted preliminary examinations in the diagnosis of the uterus and tubes. We employed an intraluminal instrument supplied by Dornier. The intraluminal transducers of this instrument have a diameter of 3.5 and 5 F. Following in-vitro examinations, hysteroscopy and laparoscopy/laparotomy were performed in 15 patients during which the transducer was pushed up via the cervix uteri to the tubes with full vision. This was successful in all 15 patients; in 9 cases the transducer could be pushed as far as the distal end. The tubal walls were examined in detail by this method and for the first time it became possible to achieve functional diagnosis of the motility of the tubes. Strictures can be visualised. The endometrium of the uterus, however, cannot as yet be diagnosed exactly by the present-day state of examination technique. If image quality can be further improved, this method will be the first to enable a functional diagnosis of the tubes and the uterus.

Endometrium↗
PubMed1992

Human interferon regulatory factor 1: intron-exon organization.

Interferon (IFN) regulatory factor 1 (IRF-1) is a transcriptional regulatory protein that mediates the transcriptional activation of the IFN-alpha and IFN-beta genes by viruses and IFNs. To characterize the mechanisms that govern the level of IRF-1 in cells, we isolated the IRF-1 gene and characterized the structure of its intronic and exonic domains and of its regulatory promoter region. A human placental genomic library was screened with an IRF-1 cDNA probe, and two clones that contained the IRF-1 gene and its 5' regulatory region were obtained. We used these clones to determine the complete nucleotide sequence for the IRF-1 gene, finding that the IRF-1 gene spanned 7.72 kb of DNA and included 10 exons and 9 introns. When the deduced amino acid sequences were compared among different species, the most conserved exons were exons 2, 3, and 4, in which the putative DNA binding domain for the IRF-1 protein is located.

Amino Acid Sequence↗
PubMed1992

Purification, characterization and inhibition by fluoride of enolase from Streptococcus mutans DSM 320523.

Enolase from Streptococcus mutans has been purified to homogeneity by a three-step procedure. As shown by analytical ultracentrifugation and polyacrylamide gel electrophoresis under denaturing conditions, the purified enzyme is an octamer with molecular weight Mr = 360 kDa, composed of eight identical subunits with Mr = 45 kDa. The kinetic parameters of S. mutans enolase in the presence of 1 mM Mg2+ are Aspec = 130 IU x mg-1 and KM = 0.44 mM as determined by steady-state experiments in the D-glycerate 2-phosphate to enolpyruvate phosphate reaction. Enzymatic activity is inhibited noncompetitively by fluoride in the range between 0 and 10 mM NaF yielding Ki = Kii = 1.39 mM, but inhibition characteristics become competitive when tested above 10 mM. In the presence of only small amounts of phosphate (0.5 mM) the inhibitory effect of fluoride is enhanced dramatically yielding Ki = 0.26 mM. Inhibition by NaPO3F is competitive with Ki = 0.9 mM, indicating that free fluoride ions in combination with phosphate are more effective in inhibiting S. mutans enolase. It can be concluded that inhibition of enolase by fluoride in combination with phosphate can influence glycolysis in S. mutans and so reduce acid production or even growth rate, thereby leading to potential anticariogenic effects.

Buffers↗
PubMed1992

Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.

PURPOSE: At the time of primary surgery, approximately 90% of all patients with breast cancer are free of metastases, but in the next 5 years almost 50% of them will relapse. We evaluated the significance of the presence of tumor cells in bone marrow of patients with primary breast cancer to investigate their predictive value for relapse. PATIENTS AND METHODS: Two hundred sixty patients with primary breast cancer were examined for tumor cells in bone marrow aspirates taken from six sites of the skeleton. After density centrifugation, cells in interphase were smeared and stained. For the immunocytologic reaction, we used a new monoclonal antibody (2E11) that was reactive with the core protein of the tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast carcinomas. RESULTS: A significant correlation was found between tumor-cell detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was found, but there was no correlation to estrogen receptor (ER) and menopausal status. Follow-up examinations showed distant metastases in 26 of 211 patients (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive cells in bone marrow, but only four occurred among the 130 patients without tumor-cell detection. CONCLUSIONS: This study suggests that tumor-cell detection in bone marrow of patients with primary breast carcinoma is a good predictor for all distant relapses (P < .0005, Cox multiple regression analysis) and provides additional information in regard to other prognostic factors. The highest predicting value for distant metastasis results from the combination of nodal status, negative PR, and tumor-cell presence in bone marrow.

Adult↗
PubMed1991

Limited proteolysis of the beta 2-dimer of tryptophan synthase yields an enzymatically active derivative that binds alpha-subunits.

Proteolytic modification of tryptophan synthase holo-beta 2-subunit from Escherichia coli at the C-terminal side of E-296 leads to an active species (E-296-nicked holo-beta 2) capable of interacting with alpha-subunits. Although this heterologous subunit interaction is rather weak, it induces an increase in catalytic efficiency in E-296-nicked holo-beta 2 by a factor of about 150. Correspondingly, enzymatic activity of alpha-subunits is enhanced 180-fold. This is in striking contrast to the findings from earlier reports which demonstrated that proteolytic derivatives modified at other positions in the "hinge region" embedded in the C-domain of the beta 2-subunit (K-272, R-275, and K-283) are enzymatically inactive and cannot associate with alpha-subunits. The equilibrium binding curve for the cofactor pyridoxal 5'-phosphate to E-296-nicked apo-beta 2 is hyperbolic (i.e., noncooperative), yielding an apparent microscopic dissociation constant, Kd, of 5 x 10(-6) M. This value closely resembles the low-affinity dissociation constant of cooperative cofactor binding to the native beta 2-subunit, indicating that the conformational interactions between structural domains in the modified beta-protein seem to be disturbed considerably.

Amino Acid Sequence↗
PubMed1991

Common infections in the history of cancer patients and controls.

The association between the frequency of manifest infectious diseases and cancer risk was investigated in a case-control study at Heidelberg, FRG. A total of 255 cases with carcinomas of the stomach, colon, rectum, breast, and ovary, as well as 255 population controls and 230 hospital controls were interviewed using a standard questionnaire. Controls were matched to the cases for age, sex, and region of residence at the time of the interview. A history of common colds or gastroenteric influenza prior to the interview was found to be associated with a decreased cancer risk. Thus the odds ratios for "three or more common colds per year (on average)" versus "no common cold within the last 5 years prior to the interview" were 0.18 (95% CI = 0.05-0.69) and 0.23 (95% CI = 0.06-0.89) relative to population controls and hospital controls, respectively. There was no apparent relationship between childhood infections or other diseases reported in the earlier history, and cancer risk. While the findings are supported by previous studies and fit well into the results of other fields of cancer research, a conclusive interpretation and biological explanation cannot yet be given.

Adult↗
PubMed1991

Metabolism of debrisoquine and susceptibility to breast cancer.

There may exist an association between the genetically determined oxidation status of the antihypertensive agent debrisoquine (DEB) and the propensity to develop tumours. The metabolism of DEB is extensive in 90% of healthy subjects (metabolic ratio = MR = 0-12.6; MR = % DEB excreted divided by % 4-hydroxy-DEB excreted) and poor in 10% (MR greater than 12.6). In patients with cancer of the lung, urinary bladder, and gastrointestinum, the percentage of high metabolizers is increased to greater than 98%. The poor metabolizer mode is almost devoid of cancer patients. It was investigated whether breast cancer patients show a similar association with respect to the oxidative status of DEB. 108 breast cancer patients and 123 women with benign gynecologic disorders received 1 tablet of 10 mg DEB orally in the evening. Urine was collected for the subsequent 8 hrs and analysed for its content of DEB and its main urinary metabolite 4-OH-DEB by means of HPLC. No decreased amount of poor metabolizers was seen in the cancer group.

Breast Neoplasms↗
PubMed1991

Chemoresistance in rat ovarian tumours.

In a cisplatin resistant subline (O-342/DPP) of an intraperitoneally growing transplantable rat ovarian tumour (O-342), intracellular glutathione (GSH) was approximately doubled (mean [S.E.] 1.5 [0.26] vs. 0.8 [0.2] nmol/10(6) cells). GSH reductase activity was higher (30.64 [4.07] vs. 20 [0.92] nmol/min per mg protein), although no difference was found for GSH-S-transferase. 24 h after exposure to cisplatin, formation of DNA interstrand cross-links was at a maximum in both lines and significantly higher in O-342 (162 [23] vs. 88 [22] rad eq). Combination treatment of O-342/DDP with buthionine sulphoximine plus cisplatin resulted in a marginal increase in survival compared with cisplatin treatment; treatment of this line with 3-aminobenzamide plus cisplatin was also superior to cisplatin alone. In the sensitive line both combinations were likewise superior to cisplatin alone. In vitro, at equimolar concentration, a new platinum complex (CTDP) was at least as active as cisplatin in both lines, which suggests a superior therapeutic index because its LD50 in mice is threefold higher than that of cisplatin. A ruthenium complex (ICR) had a higher activity in the resistant line. A titanium complex (budotitane) was not active.

Animals↗
PubMed1991

Effect of intraperitoneal recombinant human tumour necrosis factor alpha on malignant ascites.

29 patients with refractory malignant ascites due to metastatic peritoneal spread of adenocarcinomas originating from the ovary, gastrointestinal tract, liver, breast and uterus were treated in a phase I trial of intraperitoneal infusions of recombinant human tumour necrosis factor alpha (rhTNF-alpha). Patients received 40-350 micrograms/m2 rhTNF-alpha intraperitoneally once weekly for 2 months or for a shorter period in case of early resolution of ascites. Systemic side-effects resembled those reported for rhTNF-alpha given intravenously. No dose-limiting toxicities were found and thus a maximum tolerated dose of intraperitoneal rhTNF-alpha was not established. Out of 29 patients, 22 responded with a complete (16) or partial (6) resolution of their ascites. There was a less than 50% reduction in 4, and no increase in ascites in 1. 1 patient showed progressive ascites formation, and another patient was not eligible because of early death unrelated to treatment. Trials in patients with smaller tumour burden are warranted.

Adenocarcinoma↗
PubMed1991

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma.

Ecto-5'-nucleotidase (ecto-5'-NT) is a phosphatidylinositol anchored membrane structure recently defined as the lymphocyte differentiation antigen CD73. Using CD73 (1E9.28.1) monoclonal antibody, normal mammary gland and breast carcinoma were immunohistochemically investigated for ecto-5'-NT expression. In normal breast epithelium, CD73 was differentially expressed in lobular, ductal and myoepithelial cells and was most frequently detected in the myoepithelial compartment. The glandular stroma contained fibrocytes, a subset of which was also CD73-positive. Among 102 unselected breast carcinoma primary lesions, only 9 contained CD73-positive tumour cells, whereas in 95 cases, stromal fibroblasts and fibrocytes showed variable degrees of CD73 expression. The extent of stromal CD73 expression correlated positively with the estrogen receptor (ER) status of the tumour (P less than 0.038). We conclude that ecto-5'-NT-expression reflects a still unknown state of activity of normal breast epithelium which is lost in the majority of carcinomas derived therefrom. It may also be indicative of some functional activity of stromal fibroblasts which is significantly enhanced in ER-positive carcinomas.

5'-Nucleotidase↗